Expression of Cyclin Genes in Cervical Carcinomas

Cho, Jun Hyung; Cha, Soon Do; Lee, Tae Sung; Cho, Chi Heum; Baek, Won Ki; Suh, Seong Il; Suh, Min Ho

Abstract

Human papillomavirus(HPV) infection is one of the common sexual transmitted infections in Korea, and evidence that HPV plays a central role in the development of cervical cancer and its precusors is growing. HPV is a small, double stranded, non-enveloped DNA virus that infects epithelial cells, replicates within their nuclei, and causes hyperproliferative lesions. HPV type 16 and 18 are most strongly associated with high-grade lesion and cancer of the cervix. HPV DNA is integrated into the genome of the host cell in most invasive cancers. Integration usually results in disruption of the viral transcriptional regulatory circuit, which may faciliate cell proliferation by allowing deregulated expression of the viral oncogenes E6 and E7. The high risk HPV E6 protein can form complex with tumor suppressor protein p53 and faciliate the rapid degradation of p53 via the ubiquitin dependent proteolytic system. The high risk E7 protein binds pRB related proteins and then displaces E2F like transcription factors from pRB related proteins. By inactivating p53 and pRB, HPV can induce proliferation of infected cells. In order to elucidate the association between HPV infection and the expression of cyclin genes in cervical cancers, we studied the prevalence of HPV infection and the expression level of cyclin genes(cyclin A, B, C, D1 and E) in nine cervical cancer samples. The presence of HPV infection was examined by RT-PCR and restriction enzyme analysis. HPV was detected in all cases(9/9): HPV type 16 was detected in 6 cases, HPV type 18 in 2 cases and an unknown type was detected in one case. The expression level of cyclin genes were evaluated by semiquantitative RT-PCR method. Expression of examined cyclin genes(cyclin A, B, C, D1 and E) were increased in all cancer tissues, and cyclin B and C expression were remarkably increased. There are no differences of expression levels of cyclins depending on infected HPV types.